Low-Dose Radiation Therapy and Combination Chemotherapy Following Surgery in Treating Children With Newly Diagnosed Primitive Neuroectodermal Tumor or Medulloblastoma - Full Text View

Sponsor:	Children's Hospital of Philadelphia
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00031590

Purpose

RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Combining low-dose radiation therapy with combination chemotherapy may be effective in treating primitive neuroectodermal tumor and medulloblastoma.

PURPOSE: This phase II trial is studying giving low-dose radiation therapy together with combination chemotherapy after surgery to see how well it works in treating children with newly diagnosed primitive neuroectodermal tumor or medulloblastoma.

Condition	Intervention	Phase
Brain and Central Nervous System Tumors	Drug: cisplatin Drug: cyclophosphamide Drug: etoposide Drug: lomustine Drug: vincristine sulfate	Phase II

Study Type:	Interventional
Study Design:	Treatment
Official Title:	Study Of Reduced Dose Craniospinal Radiotherapy (1800 cGy) And Chemotherapy In Children With Newly-Diagnosed Standard-Risk Posterior Fossa Primitive Neuro-ectodermal Tumor (PNET/Medulloblastoma)

Resource links provided by NLM:

MedlinePlus related topics: Cancer Surgery

Drug Information available for: Cyclophosphamide Vincristine Lomustine Cisplatin Etoposide Etoposide phosphate Vincristine sulfate

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Relapse-free survival [ Designated as safety issue: No ]
Survival [ Designated as safety issue: No ]
Exoprimary-site relapse rate [ Designated as safety issue: No ]
Time to first recurrence [ Designated as safety issue: No ]
Degree of neurocognitive post-treatment decline or dysfunction as measured by an IQ test at baseline and after 1, 2, and 3 years [ Designated as safety issue: No ]
Degree of hearing loss [ Designated as safety issue: No ]
Decline in growth, sexual maturation, or need for hormone replacement [ Designated as safety issue: No ]
Adverse events [ Designated as safety issue: Yes ]

Estimated Enrollment:	50
Study Start Date:	April 2001
Estimated Primary Completion Date:	December 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Regimen A: Experimental Patients receive oral lomustine and cisplatin IV over 8 hours on day 0 and vincristine IV on days 0, 7, and 14.	Drug: cisplatin Given orally and IV Drug: lomustine Given orally and IV Drug: vincristine sulfate Given orally and IV
Regimen B: Experimental Patients receive cyclophosphamide IV on days 0 and 1 and etoposide IV on days 0 and 1 and then orally on days 14-34.	Drug: cyclophosphamide Given orally and IV Drug: etoposide Given orally and IV

Detailed Description:

OBJECTIVES:

Reduce the late cognitive, auditory, and endocrinologic effects in children with newly diagnosed standard-risk posterior fossa primitive neuroectodermal tumor or medulloblastoma by reducing the adjuvant craniospinal radiotherapy dose by 25%, but maintaining a therapeutic efficacy (86% 3-year relapse-free survival) of current standard therapy by using maintenance chemotherapy comprising lomustine, cisplatin, and vincristine alternated with cyclophosphamide and etoposide.
Evaluate the acute and subacute toxicity of this regimen in these patients.
Evaluate the late neurotoxic effects of low-dose craniospinal radiotherapy, in terms of cognitive, endocrinologic, and auditory function, in these patients.

OUTLINE: This is a multicenter study.

Adjuvant induction chemoradiotherapy: Beginning within 28 days after prior resection, patients undergo radiotherapy to the craniospinal axis 5 days a week for 2 weeks and then conformal radiotherapy to the tumor bed 5 days a week for 4 weeks. Beginning 1 week after the initiation of radiotherapy, patients receive vincristine IV weekly for 6 weeks.
Maintenance chemotherapy: Beginning 4 weeks after the completion of induction chemoradiotherapy, patients receive two 6-week courses of regimen A as outlined below alternated with one 6-week course of regimen B as outlined below for a total of 9 courses (6 courses of regimen A and 3 courses of regimen B).
- Regimen A: Patients receive oral lomustine and cisplatin IV over 8 hours on day 0 and vincristine IV on days 0, 7, and 14.
- Regimen B: Patients receive cyclophosphamide IV on days 0 and 1 and etoposide IV on days 0 and 1 and then orally on days 14-34.

Patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study within 3 years.

Eligibility

Ages Eligible for Study:	3 Years to 30 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed posterior fossa primitive neuroectodermal tumor or medulloblastoma
Standard-risk disease
- No residual tumor greater than 1.5 cm^2 after resection by postoperative MRI
- No tumor in the spinal or cerebral subarachnoid space by MRI
- No tumor in the subarachnoid space by CSF cytology
- No failure to perform staging studies (spine MRI and CSF cytology) preoperatively or postoperatively
Must begin radiotherapy on study within 28 days after surgery

PATIENT CHARACTERISTICS:

Age:

3 to 30 at initial diagnosis

Performance status:

Not specified

Life expectancy:

Not specified

Hematopoietic:

Not specified

Hepatic:

Not specified

Renal:

Not specified

Other:

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

Not specified

Chemotherapy:

No prior antitumor chemotherapy

Endocrine therapy:

Prior corticosteroids allowed

Radiotherapy:

See Disease Characteristics
No prior radiotherapy

Surgery:

See Disease Characteristics

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00031590

Locations

United States, California
Lucile Packard Children's Hospital at Stanford University Medical Center	Recruiting
Palo Alto, California, United States, 94304
Contact: Paul G. Fisher, MD, MHS 650-497-8953 pfisher@stanford.edu
United States, Georgia
Winship Cancer Institute of Emory University	Recruiting
Egleston, Georgia, United States, 30322
Contact: Anna J. Janss, MD, PhD 404-257-3480
United States, Pennsylvania
Children's Hospital of Philadelphia	Recruiting
Philadelphia, Pennsylvania, United States, 19104-4318
Contact: Peter C. Phillips, MD 215-590-3129

Sponsors and Collaborators

Children's Hospital of Philadelphia

Investigators

Study Chair:

Peter C. Phillips, MD

Children's Hospital of Philadelphia

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Children's Hospital of Philadelphia ( Peter C. Phillips )
Study ID Numbers:	CDR0000069075, CHP-693, CHP-IRB-2001-12-2301, NCI-V01-1680
Study First Received:	March 8, 2002
Last Updated:	July 21, 2009
ClinicalTrials.gov Identifier:	NCT00031590 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

untreated childhood medulloblastoma

Additional relevant MeSH terms:

Neuroectodermal Tumors, Primitive
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Neoplasms, Nerve Tissue
Lomustine
Physiological Effects of Drugs
Central Nervous System Neoplasms
Cyclophosphamide
Neoplasms by Site
Cisplatin
Neoplasms, Germ Cell and Embryonal
Therapeutic Uses
Glioma
Alkylating Agents

Etoposide
Nervous System Neoplasms
Neoplasms by Histologic Type
Mitosis Modulators
Nervous System Diseases
Vincristine
Antimitotic Agents
Immunosuppressive Agents
Pharmacologic Actions
Neuroectodermal Tumors
Neoplasms
Radiation-Sensitizing Agents
Tubulin Modulators
Myeloablative Agonists
Medulloblastoma

ClinicalTrials.gov processed this record on November 30, 2009